Addressing intimate partner violence during the COVID-19 pandemic and beyond: how radiologists can make a difference.

Faced with the COVID-19 pandemic, many countries both in Europe and across the world implemented strict stay-at-home orders. These measures helped to slow the spread of the coronavirus but also led to increased mental and physical health issues for the domestically confined population, including an increase in the occurrence of intimate partner violence (IPV) in many countries. IPV is defined as behavior that inflicts physical, psychological, or sexual harm within an intimate relationship. We believe that as radiologists, we can make a difference by being cognizant of this condition, raising an alert when appropriate and treating suspected victims with care and empathy. The aim of this Special Report is to raise awareness of IPV among radiologists and to suggest strategies by which to identify and support IPV victims. KEY POINTS: • The COVID-19 pandemic led to a marked increase in the number of intimate partner violence (IPV) cases, potentially leading to increased emergency department visits and radiological examinations. • Most IPV-related fractures affect the face, fingers, and upper trunk, and may easily be misinterpreted as routine trauma. • Radiologists should carefully review the medical history of suspicious cases, discuss the suspicion with the referring physician, and proactively engage in a private conversation with the patient, pointing to actionable resources for IPV victims.

Direct communication between radiologists and patients improves the quality of imaging reports.

OBJECTIVES: We investigate in what percentage of cases and to what extent radiological reports change when radiologists directly communicate with patients after imaging examinations. METHODS: One hundred twenty-two consecutive outpatients undergoing MRI examinations at a single center were prospectively included. Radiological reports of the patients were drafted by two radiologists in consensus using only the clinical information that was made available by the referring physicians. Thereafter, one radiologist talked directly with the patient and recorded the duration of the conversation. Afterwards, the additional information from the patient was used to reevaluate the imaging studies in consensus. The radiologists determined whether the radiological report changed based on additional information and, if yes, to what extent. The degree of change was graded on a 4-point Likert scale (1, non-relevant findings, to 4, highly relevant findings). RESULTS: Following direct communication (duration 170.9 ± 53.9 s), the radiological reports of 52 patients (42.6%) were changed. Of the 52 patients, the degree of change was classified as grade 1 for 8 patients (15.4 %), grade 2 for 27 patients (51.9%), grade 3 for 13 patients (25%), and grade 4 for 4 patients (7.7%). The reasons leading to changes were missing clinical information in 50 cases (96.2%) and the lack of additional external imaging in 2 cases (3.8%). CONCLUSIONS: Radiologists should be aware that a lack of accurate information from the clinician can lead to incorrect radiological reports or diagnosis. Radiologists should communicate directly with patients, especially when the provided information is unclear, as it may significantly alter the radiological report. KEY POINTS: • Direct communication between radiologists and patients for an average of 170's resulted in a change in the radiological reports of 52 patients (42.6%). • Of the 42.6% of cases where the reports were changed, the alterations were highly relevant (grades 3 and 4) in 32.7%, indicating major changes with significant impact towards patient management.

Near-Infrared Fluorescence Hydrogen Peroxide Assay for Versatile Metabolite Biosensing in Whole Blood.

In emergency medicine, blood lactate levels are commonly measured to assess the severity and response to treatment of hypoperfusion-related diseases (e.g., sepsis, trauma, cardiac arrest). Clinical blood lactate testing is conducted with laboratory analyzers, leading to a delay of 3 h between triage and lactate result. Here, a fluorescence-based blood lactate assay, which can be utilized for bedside testing, based on measuring the hydrogen peroxide generated by the enzymatic oxidation of lactate is described. To establish a hydrogen peroxide assay, near-infrared cyanine derivatives are screened and sulfo-cyanine 7 is identified as a new horseradish peroxidase (HRP) substrate, which loses its fluorescence in presence of HRP and hydrogen peroxide. As hydrogen peroxide is rapidly cleared by erythrocytic catalase and glutathione peroxidase, sulfo-cyanine 7, HRP, and lactate oxidase are encapsulated in a liposomal reaction compartment. In lactate-spiked bovine whole blood, the newly developed lactate assay exhibits a linear response in a clinically relevant range after 10 min. Substituting lactate oxidase with glucose and alcohol oxidase allows for blood glucose, ethanol, and methanol biosensing, respectively. This easy-to-use, rapid, and versatile assay may be useful for the quantification of a variety of enzymatically oxidizable metabolites, drugs, and toxic substances in blood and potentially other biological fluids.

Intimate partner violence crisis in the COVID-19 pandemic: how can radiologists make a difference?

KEY POINTS: • The COVID-19 crisis resulted in a variety of physical and mental health issues beyond the viral infection itself, as indicated by an increase in domestic violence.• Radiologists should be aware of typical intimate partner violence (IPV) injury patterns, actively ask potential IPV victims about the cause of injury, and be familiar with support systems for IPV victims of their institutions.• Emergency and radiology departments should review their protocols for identifying and supporting IPV victims, and train their staff to work together to implement these measures during and beyond the COVID-19 crisis.

An Investigation of PS-b-PEO Polymersomes for the Oral Treatment and Diagnosis of Hyperammonemia.

Ammonia-scavenging transmembrane pH-gradient poly(styrene)-b-poly(ethylene oxide) polymersomes are investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes are highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly do not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggests that the vesicles are probably destabilized during the dehydration of the intestinal chyme. The findings question the relevance of commonly used simulated intestinal fluids for studying vesicular stability. With the encapsulation of a pH-sensitive dye in the polymersome core, the local pH increase upon ammonia influx could be exploited to assess the ammonia concentration in the plasma of healthy and cirrhotic rats as well as in other fluids. Due to its high sensitivity and selectivity, this polymersome-based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests.

Serum albumin, total bilirubin, and patient age are independent confounders of hepatobiliary-phase gadoxetate parenchymal liver enhancement.

PURPOSE: To identify independent confounding variables of gadoxetate-enhanced hepatobiliary-phase liver MRI using multiple regression analysis. MATERIALS AND METHODS: The institutional review board generally approved retrospective analyses and all patients provided written informed consent. One hundred ten patients who underwent a standardized 3.0-T gadoxetate-enhanced liver MRI between November 2008 and June 2013 were retrospectively reviewed. The gadoxetate liver enhancement normalized to enhancement in the erector spinae muscle (relative signal enhancement, SE) was related to biochemical laboratory parameters and descriptive patient characteristics (patient age, body mass index) using non-parametric univariate correlation analysis followed by a multiple linear regression model. RESULTS: Using univariate statistics, relative SE was inversely correlated with patient age, ALP, AST, total bilirubin, gamma-glutamyltransferase, INR, model of end-stage liver disease score, and proportionally with albumin and hemoglobin (all p < 0.01). In a multiple regression analysis, total bilirubin (p = 0.001), serum albumin (p = 0.016), and patient age (p = 0.018) were independently correlated with relative liver SE (n = 110). CONCLUSION: A multiple regression analysis showed that high total bilirubin, low serum albumin, or advanced age was associated with low hepatobiliary-phase gadoxetate parenchymal liver enhancement. In these patients, the lower contrast-to-noise ratio might impair diagnostic evaluation of non-enhancing liver lesions (e.g., HCC, liver metastasis). KEY POINTS: • A multiple regression analysis identified independent confounding variables of hepatobiliary-phase gadoxetate liver enhancement. • High bilirubin, low albumin, or advanced age was associated with low enhancement. • Diagnostic evaluation might be hampered in these patients.

Bacterial contamination of ultrasound probes in different radiological institutions before and after specific hygiene training: do we have a general hygienical problem?

OBJECTIVES: Aim was to investigate hygienic conditions of ultrasound probes before and after hygiene training in radiology institutions in comparison to bacterial contamination in public places. METHODS: In three radiology departments, bacterial contamination was evaluated using baseline agar plates for cultures taken from 36 ultrasound probes. Afterwards teams were trained by a hygiene service centre and 36 ultrasound probes were routinely disinfected with regular disinfecting wipes and then evaluated. In comparison, bacterial contamination in public places (bus poles, n = 11; toilet seats, n = 10) were analysed. Plates were routinely incubated and the number of colony forming units (CFU) analysed. RESULTS: Cultures taken from the probes showed a median of 53 CFU before and 0 CFU after training (p < 0.001). Cultures taken from public places showed a median of 4 CFU from toilets and 28 from bus poles and had lower bacterial load in comparison to ultrasound probes before training (p = 0.055, toilets; p = 0.772, bus poles), without statistical significance. CONCLUSIONS: Bacterial contamination of ultrasound probes prior to hygiene training proved to be high and showed higher bacterial load than toilets seats or bus poles. Radiologists should be aware that the lack of hygiene in the field of ultrasound diagnostics puts patients at risk of healthcare-associated infections. KEY POINTS: • Hospital-associated infections are a problem for patient care. • Hygiene training of staff prevents bacterial contamination of ultrasound probes. • Disinfection of ultrasound probes is an easy method to protect patients.

Age dependence of spleen- and muscle-corrected hepatic signal enhancement on hepatobiliary phase gadoxetate MRI.

OBJECTIVES: To identify correlations of signal enhancements (SE) and SE normalized to reference tissues of the spleen, kidney, liver, musculus erector spinae (MES) and ductus hepatocholedochus (DHC) on hepatobiliary phase gadoxetate-enhanced MRI with patient age in non-cirrhotic patients. METHODS: A heterogeneous cohort of 131 patients with different clinical backgrounds underwent a standardized 3.0-T gadoxetate-enhanced liver MRI between November 2008 and June 2013. After exclusion of cirrhotic patients, a cohort of 75 patients with no diagnosed diffuse liver disease was selected. The ratio of signal intensity 20 min post- to pre-contrast administration (SE) in the spleen, kidney, liver, MES and DHC, and the SE of the kidney, liver and DHC normalized to the reference tissues spleen or MES were compared to patient age. RESULTS: Patient age was inversely correlated with the liver SE normalized to the spleen and MES SE (both p < 0.001) and proportionally with the SE of the spleen (p = 0.043), the MES (p = 0.030) and the kidney (p = 0.022). No significant correlations were observed for the DHC (p = 0.347) and liver SE (p = 0.606). CONCLUSION: The age dependence of hepatic SE normalized to the enhancement in the spleen and MES calls for a cautious interpretation of these quantification methods. KEY POINTS: • Patient age was inversely correlated with spleen- and MES-corrected liver rSE (p < 0.001). • Patient age was correlated with spleen (p = 0.043) and MES SE (p = 0.030). • Patient age may confound quantitative liver function assessment using gadoxetate-enhanced liver MRI.

Reduction in respiratory motion artefacts on gadoxetate-enhanced MRI after training technicians to apply a simple and more patient-adapted breathing command.

OBJECTIVE: To investigate whether a trained group of technicians using a modified breathing command during gadoxetate-enhanced liver MRI reduces respiratory motion artefacts compared to non-trained technicians using a traditional breathing command. MATERIALS AND METHODS: The gadoxetate-enhanced liver MR images of 30 patients acquired using the traditional breathing command and the subsequent 30 patients after training the technicians to use a modified breathing command were analyzed. A subgroup of patients (n = 8) underwent scans both by trained and untrained technicians. Images obtained using the traditional and modified breathing command were compared for the presence of breathing artefacts [respiratory artefact-based image quality scores from 1 (best) to 5 (non-diagnostic)]. RESULTS: There was a highly significant improvement in the arterial phase image quality scores in patients using the modified breathing command compared to the traditional one (P < 0.001). The percentage of patients with severe and extensive breathing artefacts in the arterial phase decreased from 33.3 % to 6.7 % after introducing the modified breathing command (P = 0.021). In the subgroup that underwent MRI using both breathing commands, arterial phase image quality improved significantly (P = 0.008) using the modified breathing command. CONCLUSION: Training technicians to use a modified breathing command significantly improved arterial phase image quality of gadoxetate-enhanced liver MRI. KEY POINTS: • A modified breathing command reduced respiratory artefacts on arterial-phase gadoxetate-enhanced MRI (P < 0.001). • The modified command decreased severe and extensive arterial-phase breathing artefacts (P = 0.021). • Training technicians to use a modified breathing command improved arterial-phase images.

Zeolite-Loaded Hydrogels as Wound pH-Modulating Dressings for Diabetic Wound Healing.

Wound pH has emerged as a promising therapeutic target in diabetic foot ulcers (DFU). Here, we aimed to develop a microparticle-loaded hydrogel for pH modulation in wound fluid. In a screen of polymeric and inorganic microparticles, zeolites were identified as pH-modulating microparticles. Zeolites were encapsulated in a calcium cross-linked alginate hydrogel, a biocompatible matrix clinically used as a wound dressing. This hydrogel potently neutralized hydroxide ions in serum-containing simulated wound fluid. These findings encourage a further development of this pH-modulating device as a molecular therapeutic system for DFUs.

Development of a Polymersome Blood Ammonia Assay Coupled with a Portable Near-Infrared Fluorometer.

Ammonia is a key biomarker in inborn and acquired liver disease. As clinical point-of-care blood ammonia assays are lacking, we developed a polymersome formulation for point-of-care blood ammonia sensing combined with a portable fluorometer. A pH-sensitive near-infrared (NIR) fluorescent dye was identified, which showed a strong fluorescence increase at acidic pH values. Building on reports on ammonia-selective PS-b-PEG polymersomes, these polymersomes were loaded with the NIR dye. These NIR fluorescent polymersomes sensed ammonia in a clinically relevant range in ammonia-spiked fresh whole blood with high linearity (R 2 = 0.9948) after 5 min using a conventional tabletop plate reader. Subsequently, the assay was tested with a portable fluorometer. An ammonia-dependent fluorescence increase was detected in ammonia-spiked fresh mouse blood after 5 min using the portable fluorometer. The NIR dye-loaded PS-b-PEG polymersomes rapidly sensed ammonia with high linearity in whole blood. This assay was successfully combined with a portable fluorometer and only required 3 µL of blood. These findings motivate a further development and clinical translation of this point-of-care blood ammonia assay.

Wound pH-Modulating Strategies for Diabetic Wound Healing.

Significance: Chronic diabetic wounds on the lower extremities (diabetic foot ulcers, DFU) are one of the most prevalent and life-threatening complications of diabetes, responsible for significant loss of quality of life and cost to the health care system. Available pharmacologic treatments fail to achieve complete healing in many patients. Recent studies and investigational treatments have highlighted the potential of modulating wound pH in DFU. Recent Advances: Data from in vitro, preclinical, and clinical studies highlight the role of pH in the pathophysiology of DFU, and topical administration of pH-lowering agents have shown promise as a therapeutic strategy for diabetic wounds. In this critical review, we describe the role of pH in DFU pathophysiology and present selected low-molecular-weight and hydrogel-based pH-modulating systems for wound healing and infection control in diabetic wounds. Critical Issues: The molecular mechanisms leading to pH alterations in diabetic wounds are complex and may differ between in vitro models, animal models of diabetes, and the human pathophysiology. Wound pH-lowering bandages for DFU therapy must be tested in established animal models of diabetic wound healing and patients with diabetes to establish a comprehensive benefit-risk profile. Future Directions: As our understanding of the role of pH in the pathophysiology of diabetic wounds is deepening, new treatments for this therapeutic target are being developed and will be tested in preclinical and clinical studies. These therapeutic systems will establish a target product profile for pH-lowering treatments such as an optimal pH profile for each wound healing stage. Thus, controlling wound bed pH could become a powerful tool to accelerate chronic diabetic wound healing.

Gender Differences in Pharmacokinetics: A Perspective on Contrast Agents.

Gender is an important risk factor for adverse drug reactions. Women report significantly more adverse drug reactions than men. There is a growing consensus that gender differences in drug PK is a main contributor to higher drug toxicity in women. These differences stem from physiological differences (body composition, plasma protein concentrations, and liver and kidney function), drug interactions, and comorbidities. Contrast agents are widely used to enhance diagnostic performance in computed tomography and magnetic resonance imaging. Despite their broad use, these contrast agents can lead to important adverse reactions including hypersensitivity reactions, nephropathy, and hyperthyroidism. Importantly, female gender is one of the main risk factors for contrast agent toxicity. As these adverse reactions may be related to gender differences in PK, this perspective aims to describe distribution and elimination pathways of commonly used contrast agents and to critically discuss gender differences in these processes.

Celiac disease: a challenging disease for pharmaceutical scientists.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects ~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influences the susceptibility of individuals towards CD, though environmental factors also play a role. With no pharmacological treatments available, the only option to keep CD in remission is a strict and permanent exclusion of dietary gluten. Such a gluten-free diet is difficult to maintain because of gluten's omnipresence in food (e.g., additive in processed food). The development of adjuvant therapies which would permit the intake of small amounts of gluten would be desirable to improve the quality of life of patients on a gluten-free diet. Such therapies include gluten-degrading enzymes, polymeric binders, desensitizing vaccines, anti-inflammatory drugs, transglutaminase 2 inhibitors, and HLA-DQ2 blockers. However, many of these approaches pose pharmaceutical challenges with respect to drug formulation and stability, or application route and dosing interval. This perspective article discusses how pharmaceutical scientists may deal with these challenges and contribute to the implementation of novel therapeutic options for patients with CD.

Vesicular Diagnostics: A Spotlight on Lactate- and Ammonia-Sensing Systems.

Liposomes are a highly successful drug delivery system with over 15 FDA-approved formulations. Beyond delivering drugs, lipid and polymer vesicles have successfully been used for diagnostic applications. These applications range from more traditional uses, such as releasing diagnostic agents in a controlled manner, to leveraging the unique membrane properties to separate analytes and provide isolated reaction compartments in complex biological matrices. In this Spotlight on Applications, I highlight the complexities in the development and translation of diagnostic vesicles with two case studies, a liposomal reaction compartment for lactate sensing and a transmembrane pH-gradient polymersome for ammonia sensing.

Real-Time Tracking of In Situ-Forming Alginate Hydrogel by Contrast-Enhanced Computed Tomography.

Hydrogel-based biomaterials have gained broad acceptance for tissue engineering and drug delivery applications. As their function generally depends on their localization, identifying the hydrogel position in the body is relevant and will alert physicians about potentially dangerous hydrogel migration. Monitoring the localization of hydrogels by imaging is challenging due to their high water content. Here, we developed a method to render alginate hydrogels visible on computed tomography (CT) and X-ray for real-time tracking of hydrogels inside the body. This method is based on physically immobilizing emulsion droplets of ethiodized oil, an FDA-approved positive CT contrast agent, in calcium-crosslinked alginate hydrogels. We prepared an oil-in-water emulsion of ethiodized oil with micron-sized emulsion droplets and encapsulated it in a calcium-crosslinked alginate hydrogel. This injectable in situ-forming hydrogel was stable for at least 2 weeks in vitro, visible on CT and X-ray in mice, and showed contrast agent concentration-dependent signal intensities. Hydrogels retrieved from mice after imaging had suitable rheological properties with a storage modulus of about 2 kPa and a loss modulus of about 0.35 kPa. This proof-of-concept study highlights the potential of ethiodized oil to localize hydrogels in real time inside the body and identifies a new use of this FDA-approved contrast agent.

Portable Near-Infrared Fluorometer for a Liposomal Blood Lactate Assay.

In sepsis, plasma lactate is a key biomarker of disease severity, prognosis, and treatment success. However, the median time to result for clinical lactate tests is 3 h. We recently reported a near-infrared fluorescent (NIRF) blood lactate assay that relies on a two-step enzymatic reaction in a liposomal reaction compartment. This assay was optimized in human blood and was capable of quantifying lactate in fresh capillary blood from human volunteers at clinically relevant concentrations in 2 min. However, these studies were performed with a tabletop fluorescence plate reader. For translation to the point of care, the liposomal lactate assay needs to be combined with a small portable NIR fluorometer. Portable NIR fluorometers were successfully used for the analysis of skin and soil samples, but reports for blood metabolite assays are scarce. We aimed at testing the performance of the liposomal lactate assay in combination with a commercial small portable NIR fluorometer. First, we tested the fluorophore of the liposomal lactate assay using the NIR dye sulfo-cyanine 7; we observed strong fluorescence signals and high linearity. Second, we performed the liposomal lactate assay in lactate-spiked human arterial blood using the portable fluorometer as the detector and observed strong and highly linear lactate sensing at clinically relevant lactate concentrations after 2 min. Finally, spiking fresh mouse blood with three clinically relevant lactate concentrations led to a significantly different response to all three concentrations after 5 min. These results highlight the usefulness of the tested portable NIR fluorometer for the liposomal lactate assay and motivate a clinical evaluation of this rapid and easy-to-use lactate assay.